This proposal seeks basic information on the transmission of pediculosis and the development of molecular-based diagnostic methods that will greatly improve and speed our ability to detect pyrethroid and lindane resistance in head lice and to better and more safely manage head louse infestations worldwide. The specific aims are: 1) using toxicokinetic and toxicodynamic approaches, determine the biochemical mechanisms underlying lindane and permethrin resistance and to elucidate additional resistance pathways; 2) Using standard PCR, cloning and sequencing techniques, identify corresponding mutations in the GABA receptor subunit gene and in the sodium channel a-subunit gene that have been shown to cause target site insensitivity resistance to lindane permethrin in other insects, respectively; and using these mutations, develop monitoring methods (SSCP, minisequencing, cPASA) for resistance management; 3) Using behavioral assays, determine the importance of direct contact versus formites in transmission; 4) Design an artificial feeding system, using a suitable membrane/blood source, enabling the rearing of pediculicide susceptible and resistant "reference strains" in the laboratory for toxicological investigations and for the determination of suitable replacement/alternative pediculicides.